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1.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
2.
Anticancer Res ; 39(8): 4149-4164, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366500

RESUMO

BACKGROUND/AIM: Signaling regulation of myeloid zinc finger 1 (MZF1) has been implicated in the progression of many human malignancies; however, the mechanistic action of MZF1 in triple-negative breast cancer (TNBC) progression remains elusive. In this study, the aim was to investigate the molecular mechanisms of MZF1 and its functional role in TNBC cellular migration and invasion. MATERIALS AND METHODS: Hs578T and MDA-MB-231 cells were transfected to stably express the acidic domain of MZF1 (MZF160-72), or were transfected with MZF1-specific or ELK1-specific short hairpin RNA (shRNA). Changes in cell morphology and distributions of cellular proteins were observed and subsequently migration and invasion were measured by wound healing and transwell assays. Expression levels of epithelial-mesenchymal transition (EMT)-related genes were carried out using immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. Data of transcriptional regulation were obtained from promoter-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS: Herein, we found that MZF1 in high-level MZF1-expressing TNBC cells is associated with cell migration, invasion, and mesenchymal phenotype. MZF1 interacted with the promoter region of insulin-like growth factor 1 receptor (IGF1R) to drive invasion and metastasis of high-level MZF1-expressing TNBC cells. Exogenous expression of the acidic domain of MZF1 repressed the binding of endogenous MZF1 to IGF1R promoter via blocking the interaction with ETS-like gene 1 (ELK1). This blockage not only caused MZF1 protein degradation, but also restrained ELK1 nuclear localization in high-level MZF1-expressing TNBC cells. MZF1, but not ELK1, was necessary for the retention of mesenchymal phenotype by repressing IGF1R promoter activity in TNBC cells expressing high levels of MZF1. Activation of the IGF1R-driven p38MAPK-ERα-slug-E-cadherin signaling axis mediated the conversion of mesenchymal cell to epithelial phenotype, caused by MZF1 destabilization. These results suggest that MZF1 is an oncogenic inducer. CONCLUSION: Blocking of the MZF1/ELK1 interaction to reduce MZF1 protein stability by saturating the endogenous MZF1/ELK1 binding domains might be a promising therapeutic strategy for the treatment of high-level MZF1-expressing TNBC.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Receptores de Somatomedina/genética , Neoplasias de Mama Triplo Negativas/genética , Proteínas Elk-1 do Domínio ets/genética , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Regiões Promotoras Genéticas/genética , Domínios Proteicos/genética , Transdução de Sinais/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
3.
Anticancer Res ; 39(8): 4325-4328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366524

RESUMO

BACKGROUND/AIM: The significance of second transurethral resection (TUR), and identification of predictive factors for residual cancer remain unrevealed. This study aimed to find residual cancer and up-staging rates, as well as predictive factors for residual cancer, in patients who undergo second TUR for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent second TURs for NMIBC between 2015 and 2017, were included in the study and their clinicopathological characteristics were analyzed for predictors of residual cancer. RESULTS: Among 143 Japanese patients whose tumors were initially diagnosed as high-risk NMIBC, residual cancers detected at second TURs were, Tis: n=22 (15.4%), Ta: n=15 (10.5%) and T1: n=29 (20.3%). No patients showed up-staging from NMIBC to MIBC. The presence of carcinoma-in situ at initial TUR was an independent risk factor for any residual cancer (Tis, Ta and T1), non-flat residual cancer (Ta and T1), and flat residual cancer (Tis). CONCLUSION: The presence of carcinoma-in situ is suggested to be an independent predictor of residual cancer. This may help guide decisions to perform second TUR.


Assuntos
Carcinoma in Situ/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Resultado do Tratamento , Uretra/patologia , Uretra/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos
4.
Anticancer Res ; 39(8): 4561-4568, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366560

RESUMO

BACKGROUND/AIM: Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. MATERIALS AND METHODS: Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. RESULTS: The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. CONCLUSION: NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Vesícula Biliar/patologia , Invasividade Neoplásica/patologia , Prognóstico , Adulto , Idoso , Antígeno CA-19-9/sangue , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
5.
Life Sci ; 234: 116771, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421084

RESUMO

AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Neoplasias Ósseas/patologia , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Animais , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Regulação para Cima , Adulto Jovem
6.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434093

RESUMO

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Assuntos
Inativação Gênica , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Caderinas/biossíntese , Adesão Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/genética
7.
Medicine (Baltimore) ; 98(27): e16009, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277094

RESUMO

Bladder cancer is one of the most common malignancies of urinary tract. The current study aimed to investigate the role of insulin-like growth factor II messenger RNA binding protein 3 (IMP3) expression in the prognostic evaluation of non-muscle- invasive urothelial carcinoma of the bladder.Immunohistochemistry (IHC) was carried out to examine IMP3 protein expression in specimens from 183 cases of non-muscle-invasive urothelial carcinoma, 20 cases of muscle-invasive urothelial carcinoma and 20 benign tissues adjacent to cancer tissue.The expression of IMP3 was not detected in the adjacent benign tissues. The expression intensity of IMP3 in muscle-invasive samples was significantly higher than that in non-muscle-invasive urothelial carcinoma specimens (P = .008). IMP3 expression was significantly related with advanced tumor stage (P < .001), advanced tumor grade (P = .004), and tumor recurrence (P < .001) in non-muscle-invasive urothelial carcinomas. Kaplan-Meier analysis showed that IMP3-positive patients had much lower disease-free (P < .001), progression-free (P = .002) and metastasis-free (P = .019) survival rates compared with those with IMP3-negative tumors. By multivariable Cox analysis, we also found that IMP3 expression in non-muscle- invasive urothelial carcinomas proved to be an independent unfavorable prognostic factor of disease-free survival (HR: 2.52; 95% CI, 1.39-4.56; P = .002), progression- free survival (HR: 5.19; 95% CI, 1.54-17.46; P = .008) and metastasis-free survival (HR: 4.87; 95% CI, 1.08-22.02; P = .040).Our results demonstrate that the expression of IMP3 in non-muscle- invasive bladder cancer can serve as an independent predictor that will help recognize the subgroup of patients with a high ability to relapse, progress, and metastasize and who might get the maximum benefit from an early and more aggressive treatment strategy.


Assuntos
Carcinoma de Células de Transição/genética , Proteínas de Ligação a RNA/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Modelos de Riscos Proporcionais , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
8.
Virchows Arch ; 475(3): 349-356, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300876

RESUMO

The Cancer Genome Atlas project introduced genomic taxonomy of basal and luminal molecular subtypes in muscle invasive bladder cancer. Fewer studies have addressed the molecular classification in non-muscle invasive bladder cancer (NMIBC). Our aim is to assess the applicability of the proposed phenotypic classification for NMIBC. Three TMAs were constructed from 193 TURBT specimens of 60 bladder cancer patients treated at one of the authors' institutions (1998-2008). Follow-up data on recurrence, grade, or stage progression was obtained. Immunohistochemistry was performed using an automated Ventana System for markers indicative of luminal (GATA3, CK20, ER, Uroplakin II, and HER2/neu) and basal (CK5/6 and CD44) phenotype. Marker expression was evaluated by 3 urologic pathologists. Using unadjusted logistic regression, we found significant association between tumor recurrence at next biopsy and CD44 expression (OR = 2.51, P = 0.03), tumor recurrence at any subsequent biopsy and ER expression (OR = 0.24, P = 0.04), and tumor grade progression at any subsequent biopsy and HER2/neu expression (OR = 0.24, P = 0.04). After adjusting for pathologic stage, we found a significant association between CK5/6 expression and tumor stage progression at either next or any subsequent biopsy (OR = 0.94, P = 0.006; and OR = 0.97, P = 0.02, respectively). Our findings suggest that individual immunohistochemical markers may be of value as prognostic factors in NMIBC.


Assuntos
Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Feminino , Fator de Transcrição GATA3/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica/métodos , Queratina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Bexiga Urinária/metabolismo , Urotélio/patologia
9.
Cancer Sci ; 110(9): 2960-2972, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301086

RESUMO

In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin-coupled microRNA capture were carried out to investigate the Ago2-dependent interaction of circCRIM1 and microRNA (miR)-93/miR-182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well-known tumor suppressor, by sponging miR-93 and miR-182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , RNA/genética , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Sci ; 110(9): 2783-2793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325403

RESUMO

Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C-C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT-qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss-of-function and gain-of-function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease-free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune-compromised and -competent mice, supporting both autonomous and non-autonomous actions of CCL22. Release of interleukin 1ß (IL-1ß) from cancer-associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF-κB). Our data support a model in which CAF-derived IL-1ß, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL-1ß-CCL22-CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Quimiocina CCL22/metabolismo , Interleucina-1beta/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Fibroblastos Associados a Câncer/imunologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Quimiocina CCL22/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/cirurgia , Neoplasias Bucais/imunologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Prognóstico , RNA Interferente Pequeno/metabolismo , Receptores CCR4/metabolismo , Transdução de Sinais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Análise de Sobrevida , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Medicine (Baltimore) ; 98(30): e16187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348230

RESUMO

BACKGROUND: Recently, many studies have been carried out to investigate the clinicopathological significance of E-cadherin expression in thyroid cancer. However, the results remained inconsistent. In the present study, we performed a meta-analysis to evaluate the associations of E-cadherin expression with susceptibility and clinicopathological characteristics of thyroid cancer. METHODS: Eligible studies were searched from Medicine, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The strength of associations between E-cadherin expression and susceptibility and clinicopathological features of thyroid cancer were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Forty-six studies with 1700 controls and 2298 thyroid cancer patients were included for this meta-analysis. Pooled results indicated that E-cadherin expression was significantly associated with susceptibility of papillary cancer and follicular cancer (papillary cancer, ORs = 14.31, 95% CIs = 3.42-59.90; follicular cancer, ORs = 10.14, 95% CI = 4.52-22.75). Significant association between E-cadherin expression and thyroid cancer risk was also observed in the subgroup analysis based on control group (normal thyroid tissue, ORs = 28.28, 95% CI = 8.36-95.63; adjacent thyroid tissue, ORs = 8.83, 95% CI = 3.27-23.85; benign thyroid tissue, ORs = 43.96, 95% CI = 9.91-194.95). In addition, E-cadherin expression was significantly correlated with lymph node metastasis, differentiation, and tumor-node-metastasis (TNM) stage of thyroid cancer (lymph node metastasis, ORs = 3.21, 95% CI = 1.98-5.20; differentiation, ORs = 0.25, 95% CI = 0.07-0.82; TNM stage, ORs = 4.85, 95% CI = 2.86-8.25). CONCLUSIONS: The present study showed that E-cadherin expression was significantly associated with susceptibility and clinicopathological characteristics of thyroid cancer, which suggested that E-cadherin expression might be a potential predictive factor for clinical progression of thyroid cancer.


Assuntos
Adenocarcinoma Folicular/patologia , Caderinas/biossíntese , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Humanos , Metástase Linfática , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Medição de Risco , Fatores de Risco
12.
Virchows Arch ; 475(3): 325-334, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201506

RESUMO

Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Tumor Carcinoide/patologia , Adenocarcinoma/patologia , Adulto , Tumor Carcinoide/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
13.
Ann R Coll Surg Engl ; 101(7): e160-e163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31219312

RESUMO

We describe a rare case of ectopic papillary thyroid cancer in the thyroglossal duct tract invading the floor-of-mouth musculature. The postablative defect was reconstructed with a bone-anchored tensor fascia lata graft to resuspend the floor of mouth to the mandible as a neogeniohyoid sling, enabling maintenance of a functional tongue position for normal speech and swallowing. This reconstruction should be considered when suprahyoid musculature is resected without breaching the oral lining.


Assuntos
Carcinoma Papilar/cirurgia , Coristoma/cirurgia , Fascia Lata/transplante , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Cisto Tireoglosso/cirurgia , Glândula Tireoide , Adulto , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Coristoma/diagnóstico , Coristoma/patologia , Feminino , Humanos , Osso Hioide/cirurgia , Imagem por Ressonância Magnética , Soalho Bucal/diagnóstico por imagem , Soalho Bucal/cirurgia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Esvaziamento Cervical/efeitos adversos , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Retalhos Cirúrgicos/transplante , Cisto Tireoglosso/diagnóstico , Cisto Tireoglosso/patologia , Tireoidectomia/efeitos adversos , Resultado do Tratamento , Adulto Jovem
14.
Nat Commun ; 10(1): 2666, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209254

RESUMO

Ran is a nucleocytoplasmic shuttle protein that is involved in cell cycle regulation, nuclear-cytoplasmic transport, and cell transformation. Ran plays an important role in cancer cell survival and cancer progression. Here, we show that, in addition to the nucleocytoplasmic localization of Ran, this GTPase is specifically associated with the plasma membrane/ruffles of ovarian cancer cells. Ran depletion has a drastic effect on RhoA stability and inhibits RhoA localization to the plasma membrane/ruffles and RhoA activity. We further demonstrate that the DEDDDL domain of Ran is required for the interaction with serine 188 of RhoA, which prevents RhoA degradation by the proteasome pathway. Moreover, the knockdown of Ran leads to a reduction of ovarian cancer cell invasion by impairing RhoA signalling. Our findings provide advanced insights into the mode of action of the Ran-RhoA signalling axis and may represent a potential therapeutic avenue for drug development to prevent ovarian tumour metastasis.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Membrana Celular/metabolismo , Neoplasias Ovarianas/patologia , Proteína ran de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica/patologia , Domínios Proteicos , Estabilidade Proteica , Proteólise , Serina/metabolismo , Transdução de Sinais , Proteína ran de Ligação ao GTP/genética
15.
Cancer Sci ; 110(8): 2658-2666, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199029

RESUMO

Although direct adhesion of cancer cells to the mesothelial cell layer is considered to be a key step for peritoneal invasion of ovarian cancer cell masses (OCM), we recently identified a different strategy for the peritoneal invasion of OCM. In 6 out of 20 cases of ovarian carcinoma, extraperitoneal growth of the OCM was observed along with the neovascularization of feeding vessels, which connect the intraperitoneal host stroma and extraperitoneal lesions through the intact mesothelial cell layer. As an early step, the OCMs anchor in the extraperitoneal fibrin networks and then induce the migration of CD34-positive and vascular endothelial growth factor A (VEGF-A)-positive endothelial cells, constructing extraperitoneal vascular networks around the OCM. During the extraperitoneal growth of OCM, podoplanin-positive and α smooth muscle actin (αSMA)-positive cancer-associated fibroblasts (CAF) appears. In more advanced lesions, the boundary line of mesothelial cells disappears around the insertion areas of feeding vessels and then extraperitoneal and intraperitoneal stroma are integrated, enabling the OCM to invade the host stroma, being associated with CAF. In addition, tissue factors (TF) are strongly detected around these peritoneal implantation sites and their levels in ascites were higher than that in blood. These findings demonstrate the presence of neovascularization around fibrin net-anchored OCMs on the outer side of the intact peritoneal surface, suggesting a novel strategy for peritoneal invasion of ovarian cancer and TF-targeted intraperitoneal anti-cancer treatment. We observed and propose a novel strategy for peritoneal implantation of ovarian cancer. The strategy includes the preinvasive growth of fibrin-anchored cancer cells along with neovascularization on the outer side of the intact peritoneal surface.


Assuntos
Fibrina/metabolismo , Invasividade Neoplásica/patologia , Neovascularização Patológica/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Ascite/metabolismo , Ascite/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Peritônio/metabolismo , Peritônio/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Medicine (Baltimore) ; 98(25): e16119, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232960

RESUMO

To compare results for radiological prediction of pathological invasiveness in lung adenocarcinoma between radiologists and a deep learning (DL) system.Ninety patients (50 men, 40 women; mean age, 66 years; range, 40-88 years) who underwent pre-operative chest computed tomography (CT) with 0.625-mm slice thickness were included in this retrospective study. Twenty-four cases of adenocarcinoma in situ (AIS), 20 cases of minimally invasive adenocarcinoma (MIA), and 46 cases of invasive adenocarcinoma (IVA) were pathologically diagnosed. Three radiologists of different levels of experience diagnosed each nodule by using previously documented CT findings to predict pathological invasiveness. DL was structured using a 3-dimensional (3D) convolutional neural network (3D-CNN) constructed with 2 successive pairs of convolution and max-pooling layers, and 2 fully connected layers. The output layer comprises 3 nodes to recognize the 3 conditions of adenocarcinoma (AIS, MIA, and IVA) or 2 nodes for 2 conditions (AIS and MIA/IVA). Results from DL and the 3 radiologists were statistically compared.No significant differences in pathological diagnostic accuracy rates were seen between DL and the 3 radiologists (P >.11). Receiver operating characteristic analysis demonstrated that area under the curve for DL (0.712) was almost the same as that for the radiologist with extensive experience (0.714; P = .98). Compared with the consensus results from radiologists, DL offered significantly inferior sensitivity (P = .0005), but significantly superior specificity (P = .02).Despite the small training data set, diagnostic performance of DL was almost the same as the radiologist with extensive experience. In particular, DL provided higher specificity than radiologists.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Aprendizado Profundo/normas , Invasividade Neoplásica/patologia , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Aprendizado Profundo/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC
17.
Cancer Sci ; 110(8): 2456-2470, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148343

RESUMO

Extracellular ATP has been shown to play an important role in invasion and the epithelial-mesenchymal transition (EMT) process in breast cancer; however, the mechanism is unclear. Here, by using a cDNA microarray, we demonstrated that extracellular ATP could stimulate hypoxia-inducible factor (HIF) signaling and upregulate hypoxia-inducible factor 1/2α (HIF-1/2α) expression. After knocking down HIF-1/2α using siRNA, we found that ATP-driven invasion and EMT were significantly attenuated via HIF2A-siRNA in breast cancer cells. By using ChIP assays, we revealed that the biological function of extracellular ATP in invasion and EMT process depended on HIF-2α direct targets, among which lysyl oxidase-like 2 (LOXL2) and matrix metalloproteinase-9 (MMP-9) mediated ATP-driven invasion, and E-cadherin and Snail mediated ATP-driven EMT, respectively. In addition, using silver staining and mass spectrometry, we found that phosphoglycerate kinase 1 (PGK1) could interact with HIF-2α and mediate ATP-driven HIF-2α upregulation. Furthermore, we demonstrated that expressions of HIF-2α and its target proteins could be regulated via ATP by AKT-PGK1 pathway. Using a Balb/c mice model, we illustrated the function of HIF-2α in promoting tumor growth and metastasis in vivo. Moreover, by exploring online databases, we found that molecules involved in ATP-HIF-2α signaling were highly expressed in human breast carcinoma tissues and were associated with poor prognosis. Altogether, these findings suggest that extracellular ATP could promote breast carcinoma invasion and EMT via HIF-2α signaling, which may be a potential target for future anti-metastasis therapy.


Assuntos
Trifosfato de Adenosina/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal/fisiologia , Hipóxia/patologia , Invasividade Neoplásica/patologia , Aminoácido Oxirredutases/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia
18.
Medicine (Baltimore) ; 98(18): e15164, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045759

RESUMO

The aim of this study was to evaluate the cytomorphologic maturity and molecular activation of cancer-associated fibroblasts (CAFs) in the intratumoral stroma and invasive front in colorectal cancer and understand how they affect cancer invasion and long-term oncological outcomes.The cytomorphologic maturity of and α-smooth muscle actin (α-SMA), fibroblast activation protein α (FAPα), and fibroblast-specific protein 1 (FSP-1) expression in CAFs in the intratumoral stroma (CAF) and the invasive front (CAF) of colorectal cancer tissues were compared (n = 147). The correlations between CAF maturation, molecular activity markers, and cancer invasion were evaluated by network analysis. Overall survival and systemic recurrence were analyzed to assess the oncological effects of CAF properties.The cytomorphologic maturation rate was comparable between CAF and CAF. The presence of mature CAFs was related to epidermal growth factor receptor overexpression in cancer cells. Expression rates of α-SMA (96.6%-98.0%) and FAPα (18.6%-22.9%) were similar between CAF and CAF. FSP-1 expression was more frequent in CAF than in CAF (66.4% vs 58.2%, P = .038). There was a significant decrease in FSP-1 expression in CAF and CAF in higher stages. The infiltrating growth pattern of the tumor was more frequent in the immature CAF. In colorectal cancer with perineural invasion and lymph node metastasis, FSP-1 expression in CAF was significantly lower. On multivariate analysis using the Cox proportional hazards model, immature CAF was found to be an independent prognostic factor of overall survival. In non-metastatic (stage I-III) colorectal cancer patients, CAF maturity was not a prognostic factor for systemic recurrence.Cytomorphologic maturity and molecular activation markers were similar between CAFs in the intratumoral stroma and invasive front of colorectal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias Colorretais/patologia , Tumores do Estroma Gastrointestinal/patologia , Invasividade Neoplásica/patologia , Actinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Receptores ErbB/metabolismo , Feminino , Tumores do Estroma Gastrointestinal/metabolismo , Gelatinases/metabolismo , Humanos , Metástase Linfática/patologia , Masculino , Proteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Serina Endopeptidases/metabolismo , Análise de Sobrevida
20.
Anticancer Res ; 39(5): 2429-2435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092435

RESUMO

BACKGROUND/AIM: Perfluorooctanoic acid (PFOA) is one of the most common perfluorinated compounds widely used in several applications. Due to its persistence in the environment, PFOA has been associated with various diseases, including cancer. This study explored the effects of PFOA on follicular thyroid carcinoma cells (FTC133). MATERIALS AND METHODS: Cell invasion, migration, adhesion and activity of matrix metalloproteinase-2 (MMP-2) were investigated using Transwell assays, adhesion assay and gelatin zymography, respectively. The underlying mechanism involved in the effects observed was evaluated by immunoblot analyses. RESULTS: Treatment with PFOA did not affect cell migration, but enhanced cell invasion, adhesion and activity of MMP-2 in FTC133 cells. PFOA selectively enhanced the phosphorylation of nuclear factor kappa B (NF-κB) p65, as well as induced NF-κB nuclear translocation. Treatment with a NF-κB inhibitor (BAY 11-7085) was able to reverse PFOA-induced cell invasiveness. CONCLUSION: PFOA promotes invasiveness of FTC133 cells mediated through the activation of NF-κB signaling.


Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Caprilatos/farmacologia , Fluorcarbonetos/farmacologia , Metaloproteinase 2 da Matriz/genética , Fator de Transcrição RelA/genética , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Nitrilos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Ativação Transcricional/efeitos dos fármacos
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